scholarly journals Polyunsaturated fatty acid-rich diets: effect on adipose tissue metabolism in rats

2001 ◽  
Vol 86 (3) ◽  
pp. 371-377 ◽  
Author(s):  
M. H. G. Gaíva ◽  
R. C. Couto ◽  
L. M. Oyama ◽  
G. E. C. Couto ◽  
V. L. F. Silveria ◽  
...  

The aim of the present study was to evaluate the effect of diets rich in n-6 and n-3 fatty acids on adipose tissue metabolism. Starting at weaning, male Wistar rats were fed ad libitum, for 8 weeks with one of the following diets: C, rat chow; S, rat chow containing 15 % (w/w) soyabean oil; F, rat chow containing 15 % (w/w) fish oil; SF, rat chow containing 15 % (w/w) soyabean and fish oil (5:1, w/w). Casein was added to the fat diets to achieve the same 20 % (w/w) protein content as in the control chow. Food intake and body weight were measured weekly. The rats were killed by decapitation and the retroperitoneal (RET) and epididymal (EPI) white adipose tissues were removed and weighed. Tissue lipid and protein content, in vivo lipogenesis rate, uptake of diet-derived lipids, in vitro lipolytic rate, adipocyte area, lipoprotein lipase, ATP citrate lyase, and malic enzyme activities were evaluated. Carcass lipid and protein contents were also measured. Energy intake was reduced while carcass lipid content was increased in the three fat-fed groups. However, carcass protein and body weight gains were elevated only with diets F and SF. Lipolysis rate was diminished by diets F and SF, while the uptake of diet-derived lipids was elevated by the diet S in both RET and EPI tissues. These metabolic alterations may have contributed to the increase in in vivo lipogenesis rate in the presence of decreased ATP citrate lyase and malic enzyme activities induced by the three lipid diets. These results indicate that enrichment of the diet with polyunsaturated fatty acids causes changes in adipose tissue metabolism that favour fat deposition. Different metabolic pathways were preferentially affected by each type of fatty acid used.

2009 ◽  
Vol 81 (3) ◽  
pp. 453-466 ◽  
Author(s):  
Cláudia M. Oller do Nascimento ◽  
Eliane B. Ribeiro ◽  
Lila M. Oyama

Approximately 40% of the total energy consumed by western populations is represented by lipids, most of them being ingested as triacylglycerols and phospholipids. The focus of this review is to analyze the effect of the type of dietary fat on white adipose tissue metabolism and secretory function, particularly on haptoglobin, TNF-α, plasminogen activator inhibitor-1 and adiponectin secretion. Previous studies have demonstrated that the duration of the exposure to the high-fat feeding, amount of fatty acid present in the diet and the type of fatty acid may or may not have a significant effect on adipose tissue metabolism. However, the long-term or short-term high fat diets, especially rich in saturated fatty acids, probably by activation of toll-like receptors, stimulated the expression of proinflammatory adipokines and inhibited adiponectin expression. Further studies are needed to investigate the cellular mechanisms by which dietary fatty acids affect white adipose tissue metabolism and secretory functions.


1999 ◽  
Vol 58 (4) ◽  
pp. 877-886 ◽  
Author(s):  
Keith N. Frayn

The metabolism of white adipose tissue is regulated by many factors, including hormones and substrates delivered in the blood, the activity of the autonomic nervous system and the rate of flow of blood through the tissue. An integrated view of adipose tissue metabolism can only be gained, therefore, from studies in vivo. Of the various techniques available for studying adipose tissue metabolism in vivo, the measurement of arterio-venous differences offers some unique possibilities. In human subjects this technique has been performed mostly by catheterization of the venous drainage of the subcutaneous abdominal depot. Studies using this technique indicate that adipose tissue has an active pattern of metabolism, responding rapidly to meal ingestion by suppressing the release of non-esterified fatty acids, or to exercise with an increase in fat mobilization. Adipose tissue blood flow may also change rapidly in these situations; for instance, it increases markedly after a meal, potentially increasing the delivery of triacylglycerol to the enzyme lipoprotein lipase (EC 3.1.1.34) for hydrolysis. During exercise, there is evidence that adipose tissue blood flow does not increase sufficiently to allow delivery of all the fatty acids released into the systemic circulation. The various adipose tissue depots have their own characteristic metabolic properties, although in human subjects these are difficult to study with the arterio-venous difference technique. A combination of tracer infusion with selective catheterization allows measurements of leg, splanchnic and non-splanchnic upper-body fat mobilization and triacylglycerol clearance. Development of such techniques may open up new possibilities in the future for obtaining an integrated picture of adipose tissue function and its depot-specific variations.


2020 ◽  
Vol 41 (6) ◽  
pp. 778-789 ◽  
Author(s):  
Su-Hyeong Kim ◽  
Eun-Ryeong Hahm ◽  
Krishna B Singh ◽  
Sruti Shiva ◽  
Jacob Stewart-Ornstein ◽  
...  

Abstract Withaferin A (WA) is a promising phytochemical exhibiting in vitro and in vivo anticancer activities against prostate and other cancers, but the mechanism of its action is not fully understood. In this study, we performed RNA-seq analysis using 22Rv1 human prostate cancer cell line to identify mechanistic targets of WA. Kyoto Encyclopedia of Genes and Genomes pathway analysis of the differentially expressed genes showed most significant enrichment of genes associated with metabolism. These results were validated using LNCaP and 22Rv1 human prostate cancer cells and Hi-Myc transgenic mice as models. The intracellular levels of acetyl-CoA, total free fatty acids and neutral lipids were decreased significantly following WA treatment in both cells, which was accompanied by downregulation of mRNA (confirmed by quantitative reverse transcription-polymerase chain reaction) and protein levels of key fatty acid synthesis enzymes, including ATP citrate lyase, acetyl-CoA carboxylase 1, fatty acid synthase and carnitine palmitoyltransferase 1A. Ectopic expression of c-Myc, but not constitutively active Akt, conferred a marked protection against WA-mediated suppression of acetyl-CoA carboxylase 1 and fatty acid synthase protein expression, and clonogenic cell survival. WA was a superior inhibitor of cell proliferation and fatty acid synthesis in comparison with known modulators of fatty acid metabolism including cerulenin and etomoxir. Intraperitoneal WA administration to Hi-Myc transgenic mice (0.1 mg/mouse, three times/week for 5 weeks) also resulted in a significant decrease in circulating levels of total free fatty acids and phospholipids, and expression of ATP citrate lyase, acetyl-CoA carboxylase 1, fatty acid synthase and carnitine palmitoyltransferase 1A proteins in the prostate in vivo.


2011 ◽  
Vol 121 (1) ◽  
pp. 19-28 ◽  
Author(s):  
Nassira Batoul Benkalfat ◽  
Hafida Merzouk ◽  
Samira Bouanane ◽  
Sid-Ahmed Merzouk ◽  
Jérôme Bellenger ◽  
...  

To investigate further the mechanisms of developmental programming, we analysed the effects of maternal overnutrition and of postnatal high-fat feeding on adipose tissue metabolism in the offspring. Postnatal changes in serum adiponectin, leptin and TAG [triacylglycerol (triglyceride)] levels, adipose tissue TAGs, fatty acids and enzyme activities were determined in offspring of cafeteria-diet-fed dams during gestation and lactation, weaned on to standard chow or on to cafeteria diet. Obese rats showed higher adiposity (+35% to 85%) as well as a significant increase in serum glucose, insulin, leptin, adiponectin and TAG levels (P<0.01) and adipose tissue LPL (lipoprotein lipase) and GPDH (glycerol-3-phosphate dehydrogenase) activities (P<0.01), compared with control pups at weaning (day 21) and at adulthood (day 90). Adipose HSL (hormone-sensitive lipase) activity was increased only at day 90 (P<0.05), and FAS (fatty acid synthase) activity remained unchanged. The proportions of SFAs (saturated fatty acids) and MUFAs (mono-unsaturated fatty acids) and the Δ9-desaturation index were significantly increased (P<0.05), whereas PUFAs (polyunsaturated fatty acids) were decreased (P<0.01) in serum and adipose TAGs of obese pups compared with controls. The cafeteria diet at weaning induced more severe abnormalities in obese rats. In conclusion, maternal overnutrition induced permanent changes in adipose tissue metabolism of the offspring. These pre-existing alterations in offspring were worsened under a high-fat diet from weaning to adulthood. Consequently, adipose adipokines and enzymes could provide a potential therapeutic target, and new investigations in this field could constitute strategies to improve the impact of early-life overnutrition.


Author(s):  
John N. Fain

AbstractThe glucocorticoid hormones alter the metabolism of the adipose tissue after an approximately 2-h lag period. The effects are mediated through the nuclear receptors that alter the expression of a wide variety of genes through the mechanisms that are similar to those seen in the other cells. There are many direct metabolic effects of the glucocorticoids on the adipose tissue metabolism, and every year, new effects are added to the list of proteins whose expression is influenced by the glucocorticoids. Furthermore, some enzymatic processes are affected by these hormones only in the presence of the other hormones such as growth hormone (GH) or insulin. Most of the effects of the glucocorticoids are on the gene transcription, and the effects on the mRNA are reflected in the altered levels of the target proteins. The glucocorticoids enhance the leptin release, while reducing that of the inflammatory adipokines and stimulating that of the lipoprotein lipase (LPL) in the presence of insulin. The activity of 11β-hydroxysteroid dehydrogenase type 1 (HSD1) is enhanced by the glucocorticoids along with that of α1 glycoprotein 1 and serum amyloid A release by the adipose tissue. In contrast, the tumor necrosis factor α (TNF)-stimulated lipolysis in the adipose tissue is blocked by the glucocorticoids. It is still unclear which, if any, of these effects account for the insulin resistance due to the glucocorticoids in the adipose tissue. However, recent work suggests that, at least in mice, the reduction in the osteocalcin release by the osteoblasts in the presence of the glucocorticoids accounts for much of the in vivo insulin resistance. In summary, there are multiple direct effects of the glucocorticoids, both anti-inflammatory and proinflammatory, on the adipose tissue.


1970 ◽  
Vol 117 (5) ◽  
pp. 861-877 ◽  
Author(s):  
B. R. Martin ◽  
R. M. Denton

1. A method is described for extracting separately mitochondrial and extramitochondrial enzymes from fat-cells prepared by collagenase digestion from rat epididymal fat-pads. The following distribution of enzymes has been observed (with the total activities of the enzymes as units/mg of fat-cell DNA at 25°C given in parenthesis). Exclusively mitochondrial enzymes: glutamate dehydrogenase (1.8), NAD–isocitrate dehydrogenase (0.5), citrate synthase (5.2), pyruvate carboxylase (3.0); exclusively extramitochondrial enzymes: glucose 6-phosphate dehydrogenase (5.8), 6-phosphogluconate dehydrogenase (5.2), NADP–malate dehydrogenase (11.0), ATP–citrate lyase (5.1); enzymes present in both mitochondrial and extramitochondrial compartments: NADP–isocitrate dehydrogenase (3.7), NAD–malate dehydrogenase (330), aconitate hydratase (1.1), carnitine acetyltransferase (0.4), acetyl-CoA synthetase (1.0), aspartate aminotransferase (1.7), alanine aminotransferase (6.1). The mean DNA content of eight preparations of fat-cells was 109μg/g dry weight of cells. 2. Mitochondria showing respiratory control ratios of 3–6 with pyruvate, about 3 with succinate and P/O ratios of approaching 3 and 2 respectively have been isolated from fat-cells. From studies of rates of oxygen uptake and of swelling in iso-osmotic solutions of ammonium salts, it is concluded that fat-cell mitochondria are permeable to the monocarboxylic acids, pyruvate and acetate; that in the presence of phosphate they are permeable to malate and succinate and to a lesser extent oxaloacetate but not fumarate; and that in the presence of both malate and phosphate they are permeable to citrate, isocitrate and 2-oxoglutarate. In addition, isolated fat-cell mitochondria have been found to oxidize acetyl l-carnitine and, slowly, l-glycerol 3-phosphate. 3. It is concluded that the major means of transport of acetyl units into the cytoplasm for fatty acid synthesis is as citrate. Extensive transport as glutamate, 2-oxoglutarate and isocitrate, as acetate and as acetyl l-carnitine appears to be ruled out by the low activities of mitochondrial aconitate hydratase, mitochondrial acetyl-CoA hydrolyase and carnitine acetyltransferase respectively. Pathways whereby oxaloacetate generated in the cytoplasm during fatty acid synthesis by ATP–citrate lyase may be returned to mitochondria for further citrate synthesis are discussed. 4. It is also concluded that fat-cells contain pathways that will allow the excess of reducing power formed in the cytoplasm when adipose tissue is incubated in glucose and insulin to be transferred to mitochondria as l-glycerol 3-phosphate or malate. When adipose tissue is incubated in pyruvate alone, reducing power for fatty acid, l-glycerol 3-phosphate and lactate formation may be transferred to the cytoplasm as citrate and malate.


1986 ◽  
Vol 64 (5) ◽  
pp. 609-614 ◽  
Author(s):  
Stephanie W. Y. Ma ◽  
David O. Foster

The net in vivo uptake or release of free fatty acids glycerol, glucose, lactate, and pyruvate by the interscapular brown adipose tissue (IBAT) of barbital-anesthetized, cold-acclimated rats was determined from measurements of plasma arteriovenous concentration differences across IBAT and tissue blood flow. Measurements were made without stimulation of the tissue and also during submaximal and maximal stimulation by infused noradrenaline (NA), the physiological activator of BAT thermogenesis. There was no appreciable uptake of glucose or release of fatty acids and glycerol by the nonstimulated tissue. At both levels of stimulation there was significant uptake of glucose (1.7 and 2.0 μmol/min) and release of glycerol (0.9 and 1.2 μmol/min), but only at maximal stimulation was there significant release of fatty acids (1.9 μmol/min). Release of lactate and pyruvate accounted for 33% of the glucose taken up at submaximal stimulation and 88% at maximal stimulation. By calculation, the remainder of the glucose taken up was sufficient to have fueled about 12% of the thermogenesis at submaximal stimulation, but only about 2% at maximal stimulation. As estimated from the rate of glycerol release, the rate of triglyceride hydrolysis was sufficient at submaximal stimulation to fuel IBAT thermogenesis entirely with the resulting fatty acids, but it was not sufficient to do so at maximal stimulation when some of the fatty acid was exported. It is suggested that at maximal NA-induced thermogenesis a portion of lipolysis proceeded only to the level of mono- and di-glycerides with the result that glycerol release did not fully reflect the rate of fatty acid formation. Both in absolute terms and in relation to the export of glycerol the in vivo export of fatty acids from the adipocytes of IBAT was much less than is observed with brown adipocytes in vitro.


2012 ◽  
Vol 302 (4) ◽  
pp. E468-E475 ◽  
Author(s):  
Keith N. Frayn ◽  
Sandy M. Humphreys

Subcutaneous abdominal adipose tissue is one of the largest fat depots and contributes the major proportion of circulating nonesterified fatty acids (NEFA). Little is known about aspects of human adipose tissue metabolism in vivo other than lipolysis. Here we collated data from 331 experiments in 255 healthy volunteers over a 23-year period, in which subcutaneous abdominal adipose tissue metabolism was studied by measurements of arterio-venous differences after an overnight fast. NEFA and glycerol were released in a ratio of 2.7:1, different ( P < 0.001) from the value of 3.0 that would indicate no fatty acid re-esterification. Fatty acid re-esterification was 10.2 ± 1.4%. Extraction of triacylglycerol (TG) (fractional extraction 5.7 ± 0.4%) indicated intravascular lipolysis by lipoprotein lipase, and this contributed 21 ± 3% of the glycerol released. Glucose uptake (fractional extraction 2.6 ± 0.3%) was partitioned around 20–25% for provision of glycerol 3-phosphate and 30% into lactate production. There was release of lactate and pyruvate, with extraction of the ketone bodies 3-hydroxybutyrate and acetoacetate, although these were small numerically compared with TG and glucose uptake. NEFA release (expressed per 100 g tissue) correlated inversely with measures of fat mass (e.g., with BMI, rs= −0.24, P < 0.001). We examined within-person variability. Systemic NEFA concentrations, NEFA release, fatty acid re-esterification, and adipose tissue blood flow were all more consistent within than between individuals. This picture of human adipose tissue metabolism in the fasted state should contribute to a greater understanding of adipose tissue physiology and pathophysiology.


1962 ◽  
Vol 25 (2) ◽  
pp. 189-198 ◽  
Author(s):  
R. M. BUCKLE

SUMMARY The quantity of free fatty acids (FFA) released from rat epididymal fat pads in vitro and their concentration within the tissue were determined. The addition of adrenaline, adrenocorticotrophic hormone (ACTH), thyroid stimulating hormone (TSH) and growth hormone (GH) each increased the release of FFA, and their respective minimum effective concentrations were 0·125, 0·004, 0·5 and 1·25 μg./ml. of medium. In every case, the increased release of FFA was associated with a rise in the quantity present within the pads, and the amount released closely paralleled their concentration within the tissue. It is suggested that the stimulatory effect of all four hormones on the release of FFA from adipose tissue is largely a manifestation of their activity of increasing the concentration of FFA within the cells, and this they do by facilitating the net conversion of storage triglyceride to fatty acid. The significance of the relative activities of the hormones in vitro is discussed and compared with their fatty acid mobilizing effects in vivo.


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